ISSN 2379-1039 Pleomorphic lobular carcinoma of breast ...

Clinical Medical & Case Reports

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ISSN2379-1039

Volume3(2017)Issue1

YadavS

OpenJClinMedCaseRep:Volume3(2017)

Pleomorphiclobularcarcinomaofbreast–cytologicalcharacteristicsanddifferentialsKavitaMunjal;SomaYadav*;DeepakAgarwal

*SomaYadav

MetropolisHealthcareLtd.India

Email:[email protected]

Abstract

Pleomorphic lobularcarcinomaofbreast(IPLC) isaveryrareanddistinctmorphologicalvariantof

invasivelobularcarcinoma(ILC),characterizedbynuclearatypiaandpleomorphismcontrastedwiththe

cytologicuniformityofILC.Alsoitisassociatedwithpoorprognosis.Thus,cytologicalrecognitionofthis

tumourisimportant.Wereportacasewiththisunusualtumourina�iftyeightyearoldfemalethat

presentedasadiagnosticdilemmaoncytology.

Introduction

Pleomorphiclobularcarcinoma(PLC)ofbreastisadistincthistologicalvariantofinvasivelobular

carcinoma(ILC)[1,2,3,4,5].Cytologicalrecognitionisimportantasthedegreeofpleomorphismexhibited

inthisspeci�icsubtypemayleadtomisinterpretationofthisparticularsubtypeoflobularcarcinomaas

in�iltratingductalcarcinoma.Also,itisassociatedwithaggressiveclinicalcourseinhavinglargersize,

markedcytologicatypia,morepronetodistantmetastasis,higherchanceoflymphovascularinvasionand

presentation at ahigher stage [6,7,8,9,10].The cytological literatureon this entity is very little.We

present a case of Pleomorphic Lobular Carcinoma diagnosed retrospectively, discuss the cytologic

featuresthatareusefulintherecognitionofthisentityandthediagnosticpitfalls.

CasePresentation

A �ifty eight year old female presented with a three month history of a self-discovered,

progressivelyincreasing,painlesspalpablelumpintheleftbreast.Shehadnosigni�icantmedicalhistory.

Therewasnofamilyhistoryofbreastdisease.Onphysicalexamination,arelativelyill-de�ined�irmmass

measuring7x6cmwaspalpableintheouterquadrant.Theoverlyingskinappearednormal.Therewas

evidenceofpalpablelymphadenopathyintheipsilateralaxilla.Mammographyreportedwell-de�ined

asymmetricdensityintheleftbreast(BIRADS-4).FineNeedleAspirationCytology(FNAC)wasdoneand

thesmearsshowedscantycellularitywithoccasionalcellsshowinglargenuclei.Asthenumberofthese

largecellswereveryfewandnoconclusioncouldbedrawnarepeataspirationwasperformedwhichwas

highly cellular with large dyscohesive cells (Figure 1a). These cells were plasmacytoid, had coarse

chromatin,inconspicuoustoprominentnucleoliandvariableamountofcytoplasm.Fewbinucleatedcells

werealsonoted.Mitotic�igureswerealsoseen(Figure1b).Thedissociatedpleomorphiccellpopulation

Keywordsaspirationcytology;breastcarcinoma;pleomorphiclobularcarcinoma

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alongwithbinucleationandmitotic�iguresledtothediagnosisofmalignancy.Basedonthisreport,wide

excisionlumpectomywithguidedwirewasperformedasthepatientwasunwillingforaradicalexcision.

Thisspecimenshowedmultipledilatedvesselswithtumourembolishowingaggregatesofmalignant

cells (Figure 2a). These cells were similar to those seen in cytology smears showing large sized

plasmacytoidcellswithmoderatetoabundantcytoplasmandeccentricallyplacedlargeroundnuclei

(Figure2b).Manybinucleatedcellswerealsonoted.Adjacentstromashowedmultiplecalci�icspherules

andperiductallymphocyticin�iltrate.Adenosis,cysticallydilatedductsandfocalepithelialhyperplasia

was also noted. No primary foci of tumour were seen. Immunohistochemistry (IHC) workup was

performedon this specimen.Tumourcellswerepositive forPanCK(Figure3a),CK7andGCDFP-15

(Figure3b)andwerenegativeforE-cadherin(Figure3c),ERandPR.CD138andLCAwerealsonegative.

Thetumourcellsalsoshowed3+positivityforHer2-neu(Figure3d).AdiagnosisofPleomorphicLobular

carcinoma was given. The patient underwent Modi�ied Radical Mastectomy (MRM) with axillary

clearance,MRMspecimenwasreceivedwhichaftercarefulgrossingandsectioningshowedtwosmallfoci

of around 1cm eachwhich onmicroscopy showed tumour cells with similarmorphology as in the

lumpectomyspecimen.Nineoutoftwelvelymphnodesalsoshowedtumourmetastasis.

Discussion

The origin of PLC has been a matter of controversy because of the morphology and

immunophenotypic characteristics that overlap between ILC and invasive ductal carcinoma. The

histological architecture and pattern of tissue invasion closely resembles ILC; however the cellular

pleomorphismandnuclearatypiaaremoreconsistentwithIDC.Infact,someauthorshavesuggestedthat

PLCisahighgradeIDCthathaslostE-cadherinexpression.

Itpredominantlyaffectspostmenopausalwomenbetweentheagesof60-80years.[8,11,12]But

thoseassociatedwithBRCAmaypresentatayoungerage[13,14].Thismayexplainthedatathatwhich

saysthatPLCmayoccuroverawideagerange,varyingfrom35to80yearsofage[8].

ImportanceofdiagnosingPLCliesinthefactthatpatientwithPLCaremorelikelytodevelop

distantmetastasis and recurrence than thosewith classical forof ILC thusassociatedwithapoorer

outcome[6].However,itremainstobedetermined,whetherthepleomorphichistologyindependently

predictsaworseoutcomeorotherknownassociatednegativeprognosticfactorssuchaslargertumor

size, increased metastatic disease, and associated worse molecular subtypes commonly present in

pleomorphiccarcinomaaccountforthepoorprognosis[23,24].

Theclinicalandhistopathologicalfeaturesofthecasesofpleomorphiclobularcarcinomaofbreast

describedsofar,havebeensummarizedinTable1.

ThecytologyofPLCishybridbetweenlobularandductalcarcinoma[18,19,20,21].Thesmearsare

cellularwith individual cell being 2-3 times the size of cells in classical ILC,withmoderate nuclear

pleomorphism,prominentnucleoliandmoderatetoabundanteosinophilic,granularto�inelyvacuolated

cytoplasm.Multinucleatedmalignantcellsmaybeseenandmitosisisfrequent[10,15].Becauseofthe

degreeofpleomorphismandtendencytoformoccasionalaggregatesinsmallgroups,distinguishingit

fromhighgradeductalcarcinomacanbechallengingattimes[16].Ourcasedemonstratedplasmacytoid

cells due to eccentric nuclear location. Thedifferential for plasmacytoid cells in the breast cytology

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includesILCanditspleomorphicvariant,IDCincludingitsapocrinetype,plasmacytoma,carcinomawith

endocrine differentiation and rarely granular cell tumours [17,18,19,20,21,22]. A higher nucleo-

cytoplasmicratio,absenceofcytoplasmicgranularityandnegativeGCDFP-15stainingaredistinguishing

featuresinfavourofIDC.Apocrinechangeissometimesfocallyseeninductalandlobularcarcinomabut

pureapocrinecarcinomasarerare(<1%).LikePLCtheyareGCDFPpositivebutareE-cadherinpositive

andmaybedistinguishedfromPLCbytheeosinophilicmacronucleoli,lackofintracytoplasmiclumina

and the solid/ comedogrowth pattern on histopathology. Plasmacytoma show a perinuclear hof,

cartwheelchromatinandlackofintracytoplasmicmucinthatmayhelptodifferentiatethemfromPLC.

Although,multinucleation,mitosisandpleomorphismmaybeseensimilartoPLC.Endocrinecarcinoma

ofbreastmayalsoshowplasmacytoidcells.Howeverthesecellsaresmaller,oflownucleargrade,have

thetypicalsaltandpepperchromatin,accentuationofstaininginparanuclearregionduetoaggregation

ofdensecoregranulesdetectedbyEMandpositivityforneuroendocrinemarkers.Theraregranularcell

tumoursofthebreastpossessgranularcytoplasmduetointarcytoplasmiclysosomes.Thetumourcells

areofschwanniandifferentiationandexpressS100.ThehistologyofPLCretainsthedistinctivegrowth

patternofILCbutshowsmarkedcellularatypia,nuclearpleomorhpismwithanincreasedmitoticrate

andmayshowsignetringcellsand/orshowapocrineorhistiocytoiddifferentiation.

Conclusion

Inconclusion,PLCmaybeachallengingdiagnosticdilemmaincytologyandrequireexperience

andregularexposuretobreastFNAC.Suboptimalyield,asinourcase,maybeacompoundingfactor.Its

behavioraldifferenceslikeincreasedrecurrence,multifocalityandbilateralitymarktheimportanceof

its recognition and differentiation from IDC as well as ILC. A thorough knowledge of the

cytohistomorphologicalfeaturesandahighdegreeofsuspicionisrequiredtodiagnosePLC.Incases

presentingasdilemma,histopathologyandimmunohistochemistrycomesinhandy.

Figures

Figure1a:On�ine-needleaspirationbiopsy,smearsarecellularwithpredominantlydyshesivemalignantcells.Tumor cells are plasmacytoid, eccentric nucleuswithprominent nucleoli and abundant cytoplasm. (MGG,x400)

Figure1b:Multinucleationandatypicalmitotic�igurenoted.(MGG,x400)

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Figure 2a: Tumour emboli seen in multiple dilatedvessels.(H&E,x400)

Figure2b:Tumourcellsarelargesizedplasmacytoidwi th moderate to abundant cytop lasm andeccentricallyplacedlargeroundnuclei.(H&E,x100)

Figure 3a: PanCK: Immunostain shows positivecystoplasmicmembranestaining.(x400)

Figure 3b: GCDFP-15: Immunostain shows positivecytoplasmicstaining.(x100)

Figure 3c: E-cadherin: Immunostain for E-cadherinshowsabsenceofmembranousstaining.(x100)

Figure3d:Her2-neu:Immunostainshows3+positivestaining.(x400)

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Table

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23:1167-71.

3. Eusebi V,Magalhaes F, Azzopardi JG. Pleomorphic lobular carcinoma of the breast: an aggressive tumour

showingapocrinedifferentiation.HumPathol1992;23:655-62.

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immunochemistryandmolecularanalysis.AmJSurgPathol2000;24:1650-6.

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Table1:Clinicalandhistopathologicalfeaturesofpleomorphiclobularcarcinomaofthebreastreportedsofar:

Age Sex Lateralization Size ER/PR/Her2neu

E-Cadherin Lymphnodestatus

Zahiretal(2013)

68 M Left 2.8x2.5cm +/+/+ - +

Ishidaetal(2013)

76 M Right 3x2.5cm +/-/- - -

Guptaetal(2012)

34 F Left 2x1.5cm -/-/- Notmentioned -

Manuchaetal(2011)

67 F Left Twofoci:1.1.7cm2.1.5cm

-/-/- - -

Rohinietal(2010)

55 M Left 3x2.5cm Notmentioned - -

Augustineetal(2007)(Threecases)

1.30

2.28

3.70

F

F

F

Left

Left

Left

4cm

10cm

Biopsyspecimen

Notmentioned

Notmentioned

Notmentioned

Notmentioned

Notmentioned

Notmentioned

+

+

Notassessed

Malyetal(2005)

44 M Left 2.5x2cm +/+/- - -

Presentcase

58 F Left 7x6cm -/-/+ - +

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ManuscriptInformation:Received:November02,2016;Accepted:January09,2017;Published:January11,2017

1 1 3AuthorsInformation:KavitaMunjal ;SomaYadav *;DeepakAgarwal

1MetropolisHealthcareLtd.India2SriAurobindoInstituteofMedicalSciences,India

Citation: Munjal K, Yadav S, Agarwal D. Pleomorphic lobular carcinoma of breast – cytological characteristics and

differentials.OpenJClinMedCaseRep.2017;1208

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